Field of the Invention
The present invention relates to a treatment of dysbiosis, a treatment of disease states caused or made worse by the presence of dysbiosis, and a novel treatment composition. In particular, it relates to the use of a small particle size salsalate as a treatment for dysbiosis.
Description of Related Art
The human colonic microbiota is a highly complex microbial ecosystem, and several hundred different species of bacteria are known to colonize the gut. The homeostasis established between the human and the resident gut bacteria plays important functional roles, such as protection against pathogenic organisms, maturation and modulation of the immune system, intestinal maturation, production of short-chain fatty acids (SCFA), mucosal physiology, and the production of vitamins, such as vitamin K and biotin. Alterations in this homeostasis, called dysbiosis, have a profound impact on human health, as demonstrated in several gastrointestinal diseases, including inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and colorectal cancer (CRC). For instance, in genetically predisposed subjects, bacterial dysbiosis, including a decrease of Firmicutes, could result in disordered innate immune reactions and lead to IBD. Dysbiosis most commonly involves the human digestive tract and is associated with numerous pathologies, including bowel disease, chronic fatigue syndrome, myalgic encepthalomyelitis/chronic fatigue syndrome, obesity, bacterial vaginosis related cancer, nonalcoholic steatohepatitis (NASH), sleep disorders, atopic dermatitis, hypertension associated with obstructive sleep apnea, cardiovascular inflammation associated with obstructive sleep apnea, enteritis-related arthritis, sleep disorder, and celiac disease (“Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome;” Gilotreaux, L. et al.s Microbiome 2016).
Bacterial dysbiosis is related to many different kinds of pathologies. The clearest correlation between dysbiosis and disease was found with inflammatory bowel diseases (IBD), wherein the proportion of Firmicutes, in particular Faecalibacterium prausnitzii (F.p.), was found to be low in patients that exhibited endoscopic recurrence six months after surgery. IBD, including Crohn's disease and ulcerative colitis, are characterized by an abnormal activation of the immune system associated with the gut, resulting in a chronic inflammation of the digestive system. Therefore, treatment and correction of dysbiosis could be of immense benefit to treating those disease states which are caused by or made worse by a patient having dysbiosis due, in main part, to decreased levels of F.p.
Salsalate is a medication that belongs to the salicylate and non-steroidal anti-inflammatory drug (NSAID) classes. Relative to other NSAIDs, salsalate has a weak inhibitory effect on the cyclooxygenase enzyme and decreases the production of several proinflammatory chemical signals, such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP). The mechanism through which salsalate is thought to reduce the production of these inflammatory chemical signals is through the inhibition of kappa B (κB) kinase, resulting in decreased action of NF-κB targeted genes. This mechanism is thought to be responsible for salsalate's insulin-sensitizing and blood sugar lowering properties. Known formulations of salsalate have an average particle size of at least around 40 microns (or more) based on the current technology for the production of salsalate.